Second special section on systems and control research efforts against COVID-19 and future pandemics
Smart testing and selective quarantine for the control of epidemics
This paper is based on the observation that, during Covid-19 epidemic, the choice of which individuals should be tested has an important impact on the effectiveness of selective confinement measures. This decision problem is closely related to the problem of optimal sensor selection, which is a very active research subject in control engineering. The goal of this paper is to propose a policy to smartly select the individuals to be tested. The main idea is to model the epidemics as a stochastic dynamic system and to select the individual to be tested accordingly to some optimality criteria, e.g. to minimize the probability of undetected asymptomatic cases. Every day, the probability of infection of the different individuals is updated making use of the stochastic model of the phenomenon and of the information collected in the previous days. Simulations for a closed community of 10'000 individuals show that the proposed technique, coupled with a selective confinement policy, can reduce the spread of the disease while limiting the number of individuals confined if compared to the simple contact tracing of positive and to an off-line test selection strategy based on the number of contacts.
Crowd management COVID-19
Crowds are a source of transmission in the COVID-19 spread. Contention and mitigation measures have focused on reducing people's mass gathering. Such efforts have led to a drop in the economy. The application of a vaccine at a world level represents a grand challenge for humanity, and it is not likely to accomplish even within months. In the meantime, we still need tools to allow the people integration into their regular routines reducing the risk of infection. In this context, this paper presents a solution for crowd management. The aim is to monitor and manage crowd levels in interior places or point-of-interests (POI), particularly shopping centers or stores. The solution is based on a POI recommendation system that suggests the nearest safe options upon request of a particular POI to visit by the user. In this sense, it recommends places near the user location with the least estimated crowd. The recommendation algorithm uses a top-K approach and behavioral game theory to predict the user's choice and estimate the crowd level for the requested POI. To evaluate the efficiency of this technological intervention in terms of the potential number of contacts of possible COVID-19 infections and the recommendation quality, we have developed an agent-based model (ABM). The adoption level of new technologies can be related to the end-user experience and trust in such technologies. As the end-user follows a recommendation that leads to uncrowded places, both the end-user experience and trust increased. We study and model this process using the OCEAN model of personality. The results from the studied scenarios showed that the proposed solution is widely adopted by the agents, as the trust factor increased from 0.5 (initial set value) to 0.76. In terms of crowd level, these are effectively managed and reduced on average by 40%. The mobility contacts were reduced by 40%, decreasing the risk of COVID-19 infection. An APP has been designed to support the described crowd management and contact tracing functionality. This APP is available on GitHub.
Forecasting COVID-19 cases based on a parameter-varying stochastic SIR model
We address the prediction of the number of new cases and deaths for the coronavirus disease 2019 (COVID-19) over a future horizon from historical data (forecasting). We use a model-based approach based on a stochastic Susceptible-Infections-Removed (SIR) model with time-varying parameters, which captures the evolution of the disease dynamics in response to changes in social behavior, non-pharmaceutical interventions, and testing rates. We show that, in the presence of asymptomatic cases, such model includes internal parameters and states that cannot be uniquely identified solely on the basis of measurements of new cases and deaths, but this does not preclude the construction of reliable forecasts for future values of these measurements. Such forecasts and associated confidence intervals can be computed using an iterative algorithm based on nonlinear optimization solvers, without the need for Monte Carlo sampling. Our results have been validated on an extensive COVID-19 dataset covering the period from March through December 2020 on 144 regions around the globe.
Optimal design of lock-down and reopening policies for early-stage epidemics through SIR-D models
The diffusion of COVID-19 represents a real threat for the health and economic system of a country. Therefore the governments have to adopt fast containment measures in order to stop its spread and to prevent the related devastating consequences. In this paper, a technique is proposed to optimally design the lock-down and reopening policies so as to minimize an aggregate cost function accounting for the number of individuals that decease due to the spread of COVID-19. A constraint on the maximal number of concomitant infected patients is also taken into account in order to prevent the collapse of the health system. The optimal procedure is built on the basis of a simple SIR model that describes the outbreak of a generic disease, without attempting to accurately reproduce all the COVID-19 epidemic features. This modeling choice is motivated by the fact that the containing measurements are actuated during the very first period of the outbreak, when the characteristics of the new emergent disease are not known but timely containment actions are required. In fact, as a consequence of dealing with poor preliminary data, the simplest modeling choice is able to reduce unidentifiability problems. Further, the relative simplicity of this model allows to compute explicitly its solutions and to derive closed-form expressions for the maximum number of infected and for the steady-state value of deceased individuals. These expressions can be then used to design static optimization problems so to determine the (open-loop) optimal lock-down and reopening policies for early-stage epidemics accounting for both the health and economic costs.
Developing control-theoretic objectives for large-scale brain dynamics and cognitive enhancement
The development of technologies for brain stimulation provides a means for scientists and clinicians to directly actuate the brain and nervous system. Brain stimulation has shown intriguing potential in terms of modifying particular symptom clusters in patients and behavioral characteristics of subjects. The stage is thus set for optimization of these techniques and the pursuit of more nuanced stimulation objectives, including the modification of complex cognitive functions such as memory and attention. Control theory and engineering will play a key role in the development of these methods, guiding computational and algorithmic strategies for stimulation. In particular, realizing this goal will require new development of frameworks that allow for controlling not only brain activity, but also latent dynamics that underlie neural computation and information processing. In the current opinion, we review recent progress in brain stimulation and outline challenges and potential research pathways associated with exogenous control of cognitive function.
Data-driven methods for present and future pandemics: Monitoring, modelling and managing
This survey analyses the role of data-driven methodologies for pandemic modelling and control. We provide a roadmap from the access to epidemiological data sources to the control of epidemic phenomena. We review the available methodologies and discuss the challenges in the development of data-driven strategies to combat the spreading of infectious diseases. Our aim is to bring together several different disciplines required to provide a holistic approach to epidemic analysis, such as data science, epidemiology, and systems-and-control theory. A 3M-analysis is presented, whose three pillars are: Monitoring, Modelling and Managing. The focus is on the potential of data-driven schemes to address three different challenges raised by a pandemic: (i) monitoring the epidemic evolution and assessing the effectiveness of the adopted countermeasures; (ii) modelling and forecasting the spread of the epidemic; (iii) making timely decisions to manage, mitigate and suppress the contagion. For each step of this roadmap, we review consolidated theoretical approaches (including data-driven methodologies that have been shown to be successful in other contexts) and discuss their application to past or present epidemics, such as Covid-19, as well as their potential application to future epidemics.
On an interval prediction of COVID-19 development based on a SEIR epidemic model
In this paper, a new version of the well-known epidemic mathematical SEIR model is used to analyze the pandemic course of COVID-19 in eight different countries. One of the proposed model's improvements is to reflect the societal feedback on the disease and confinement features. The SEIR model parameters are allowed to be time-varying, and the ranges of their values are identified by using publicly available data for France, Italy, Spain, Germany, Brazil, Russia, New York State (US), and China. The identified model is then applied to predict the SARS-CoV-2 virus propagation under various conditions of confinement. For this purpose, an interval predictor is designed, allowing variations and uncertainties in the model parameters to be taken into account. The code and the utilized data are available on Github.
Modeling and control of epidemics through testing policies
Testing is a crucial control mechanism in the beginning phase of an epidemic when the vaccines are not yet available. It enables the public health authority to detect and isolate the infected cases from the population, thereby limiting the disease transmission to susceptible people. However, despite the significance of testing in epidemic control, the recent literature on the subject lacks a control-theoretic perspective. In this paper, an epidemic model is proposed that incorporates the testing rate as a control input and differentiates the undetected infected from the detected infected cases, who are assumed to be removed from the disease spreading process in the population. After estimating the model on the data corresponding to the beginning phase of COVID-19 in France, two testing policies are proposed: the so-called best-effort strategy for testing (BEST) and constant optimal strategy for testing (COST). The BEST policy is a suppression strategy that provides a minimum testing rate that stops the growth of the epidemic when implemented. The COST policy, on the other hand, is a mitigation strategy that provides an optimal value of testing rate minimizing the peak value of the infected population when the total stockpile of tests is limited. Both testing policies are evaluated by their impact on the number of active intensive care unit (ICU) cases and the cumulative number of deaths for the COVID-19 case of France.
Hysteresis-based supervisory control with application to non-pharmaceutical containment of COVID-19
The recent COVID-19 outbreak has motivated an extensive development of non-pharmaceutical intervention policies for epidemics containment. While a total lockdown is a viable solution, interesting policies are those allowing some degree of normal functioning of the society, as this allows a continued, albeit reduced, economic activity and lessens the many societal problems associated with a prolonged lockdown. Recent studies have provided evidence that fast periodic alternation of lockdown and normal-functioning days may effectively lead to a good trade-off between outbreak abatement and economic activity. Nevertheless, the correct number of normal days to allocate within each period in such a way to guarantee the desired trade-off is a highly uncertain quantity that cannot be fixed a priori and that must rather be adapted online from measured data. This adaptation task, in turn, is still a largely open problem, and it is the subject of this work. In particular, we study a class of solutions based on hysteresis logic. First, in a rather general setting, we provide general convergence and performance guarantees on the evolution of the decision variable. Then, in a more specific context relevant for epidemic control, we derive a set of results characterizing robustness with respect to uncertainty and giving insight about how a priori knowledge about the controlled process may be used for fine-tuning the control parameters. Finally, we validate the results through numerical simulations tailored on the COVID-19 outbreak.
Convex output feedback model predictive control for mitigation of COVID-19 pandemic
In this paper, a model predictive control approach is proposed for epidemic mitigation. The disease spreading dynamics is described by an 8-compartment smooth nonlinear model of the COVID-19 pandemic in Hungary known from the literature, where the manipulable control input is the stringency of the introduced non-pharmaceutical measures. It is assumed that only the number of hospitalized people is measured on-line, and the other state variables are computed using a state observer which is based on the dynamic inversion of a linear sub-system of the model. The objective function contains a measure of the direct harmful consequences of the restrictions, and the constraints refer to input bounds and to the capacity of the healthcare system. By exploiting the special properties of the model, the nonlinear optimization problem required by the control design is reformulated to convex tasks, allowing a computationally efficient solution. Two approaches are proposed: the first finds a suboptimal solution by geometric programming, while the second one further simplifies the problem and transforms it to a linear programming task. Simulations show that both suboptimal solutions fulfill the design specifications even in the presence of parameter uncertainties.
Third special section on systems and control research efforts against COVID-19 and future pandemics
COVID-19 epidemic control using short-term lockdowns for collective gain
While many efforts are currently devoted to vaccines development and administration, social distancing measures, including severe restrictions such as lockdowns, remain fundamental tools to contain the spread of COVID-19. A crucial point for any government is to understand, on the basis of the epidemic curve, the right temporal instant to set up a lockdown and then to remove it. Different strategies are being adopted with distinct shades of intensity. USA and Europe tend to introduce restrictions of considerable temporal length. They vary in time: a severe lockdown may be reached and then gradually relaxed. An interesting alternative is the Australian model where short and sharp responses have repeatedly tackled the virus and allowed people a return to near normalcy. After a few positive cases are detected, a lockdown is immediately set. In this paper we show that the Australian model can be generalized and given a rigorous mathematical analysis, casting strategies of the type in the context of , an important branch of nonlinear control theory. This allows us to gain important insights regarding how to implement short-term lockdowns, obtaining a better understanding of their merits and possible limitations. Effects of vaccines administration in improving the control law's effectiveness are also illustrated. Our model predicts the duration of the severe lockdown to be set to maintain e.g. the number of people in intensive care under a certain threshold. After tuning our strategy exploiting data collected in Italy, it turns out that COVID-19 epidemic could be e.g. controlled by alternating one or two weeks of complete lockdown with one or two months of freedom, respectively. Control strategies of this kind, where the lockdown's duration is well circumscribed, could be important also to alleviate coronavirus impact on economy.
A time-modulated Hawkes process to model the spread of COVID-19 and the impact of countermeasures
Motivated by the recent outbreak of coronavirus (COVID-19), we propose a stochastic model of epidemic temporal growth and mitigation based on a time-modulated Hawkes process. The model is sufficiently rich to incorporate specific characteristics of the novel coronavirus, to capture the impact of undetected, asymptomatic and super-diffusive individuals, and especially to take into account time-varying counter-measures and detection efforts. Yet, it is simple enough to allow scalable and efficient computation of the temporal evolution of the epidemic, and exploration of what-if scenarios. Compared to traditional compartmental models, our approach allows a more faithful description of virus specific features, such as distributions for the time spent in stages, which is crucial when the time-scale of control (e.g., mobility restrictions) is comparable to the lifetime of a single infection. We apply the model to the first and second wave of COVID-19 in Italy, shedding light onto several effects related to mobility restrictions introduced by the government, and to the effectiveness of contact tracing and mass testing performed by the national health service.
Dynamical characterization of antiviral effects in COVID-19
Mathematical models describing SARS-CoV-2 dynamics and the corresponding immune responses in patients with COVID-19 can be critical to evaluate possible clinical outcomes of antiviral treatments. In this work, based on the concept of virus spreadability in the host, antiviral effectiveness thresholds are determined to establish whether or not a treatment will be able to clear the infection. In addition, the virus dynamic in the host - including the time-to-peak and the final monotonically decreasing behavior - is characterized as a function of the time to treatment initiation. Simulation results, based on nine patient data, show the potential clinical benefits of a treatment classification according to patient critical parameters. This study is aimed at paving the way for the different antivirals being developed to tackle SARS-CoV-2.
Monitoring and forecasting the COVID-19 epidemic in the UK
This paper shows how existing methods of time series analysis and modeling can be exploited in novel ways to monitor and forecast the COVID-19 epidemic. In the past, epidemics have been monitored by various statistical and model metrics, such as evaluation of the effective reproduction number, . However, can be difficult and time consuming to compute. This paper suggests two relatively simple data-based metrics that could be used in conjunction with estimation and provide rapid indicators of how the epidemic's dynamic behavior is progressing. The new metrics are the epidemic rate of change (RC) and a related state-dependent response rate parameter (RP), recursive estimates of which are obtained from dynamic harmonic and dynamic linear regression (DHR and DLR) algorithms. Their effectiveness is illustrated by the analysis of COVID-19 data in the UK and Italy. The paper also shows how similar methodology, combined with the refined instrumental variable method for estimating hybrid Box-Jenkins models of linear dynamic systems (RIVC), can be used to relate the daily death numbers in the Italian and UK epidemics and then provide 15-day-ahead forecasts of the UK daily death numbers. The same approach can be used to model and forecast the UK epidemic based on the daily number of COVID-19 patients in UK hospitals. Finally, the paper speculates on how the state-dependent parameter (SDP) modeling procedures may provide data-based insight into a nonlinear differential equation model for epidemics such as COVID-19.
Multitask learning and nonlinear optimal control of the COVID-19 outbreak: A geometric programming approach
We propose a multitask learning approach to learn the parameters of a compartmental discrete-time epidemic model from various data sources and use it to design optimal control strategies of human-mobility restrictions that both curb the epidemic and minimize the economic costs associated with implementing non-pharmaceutical interventions. We develop an extension of the SEIR epidemic model that captures the effects of changes in human mobility on the spread of the disease. The parameters of the model are learned using a multitask learning approach that leverages both data on the number of deaths across a set of regions, and cellphone data on individuals' mobility patterns specific to each region. Using this model, we propose a nonlinear optimal control problem aiming to find the optimal mobility-based intervention strategy that curbs the spread of the epidemic while obeying a budget on the economic cost incurred. We also show that the solution to this nonlinear optimal control problem can be efficiently found, in polynomial time, using tools from geometric programming. Furthermore, in the absence of a straightforward mapping from human mobility data to economic costs, we propose a practical method by which a budget on economic losses incurred may be chosen to eliminate excess deaths due to over-utilization of hospital resources. Our results are demonstrated with numerical simulations using real data from the COVID-19 pandemic in the Philadelphia metropolitan area.
The Ockham's razor applied to COVID-19 model fitting French data
This paper presents a data-based simple model for fitting the available data of the Covid-19 pandemic evolution in France. The time series concerning the 13 regions of mainland France have been considered for fitting and validating the model. An extremely simple, two-dimensional model with only two parameters demonstrated to be able to reproduce the time series concerning the number of daily demises caused by Covid-19, the hospitalizations, intensive care and emergency accesses, the daily number of positive tests and other indicators, for the different French regions. These results might contribute to stimulate a debate on the suitability of much more complex models for reproducing and forecasting the pandemic evolution since, although relevant from a mechanistic point of view, they could lead to nonidentifiability issues.
Universal features of epidemic models under social distancing guidelines
Social distancing as a form of nonpharmaceutical intervention has been enacted in many countries as a form of mitigating the spread of COVID-19. There has been a large interest in mathematical modeling to aid in the prediction of both the total infected population and virus-related deaths, as well as to aid government agencies in decision making. As the virus continues to spread, there are both economic and sociological incentives to minimize time spent with strict distancing mandates enforced, and/or to adopt periodically relaxed distancing protocols, which allow for scheduled economic activity. The main objective of this study is to reduce the disease burden in a population, here measured as the peak of the infected population, while simultaneously minimizing the length of time the population is socially distanced, utilizing both a single period of social distancing as well as periodic relaxation. We derive a linear relationship among the optimal start time and duration of a single interval of social distancing from an approximation of the classic epidemic model. Furthermore, we see a sharp phase transition region in start times for a single pulse of distancing, where the peak of the infected population changes rapidly; notably, this transition occurs well one would intuitively expect. By numerical investigation of more sophisticated epidemiological models designed specifically to describe the COVID-19 pandemic, we see that all share remarkably similar dynamic characteristics when contact rates are subject to periodic or one-shot changes, and hence lead us to conclude that these features are in epidemic models. On the other hand, the nonlinearity of epidemic models leads to non-monotone behavior of the peak of infected population under periodic relaxation of social distancing policies. This observation led us to hypothesize that an additional single interval social distancing at a can significantly decrease the infected peak of periodic policies, and we verified this improvement numerically. While synchronous quarantine and social distancing mandates across populations effectively minimize the spread of an epidemic over the world, relaxation decisions should not be enacted at the same time for different populations.
Robust and optimal predictive control of the COVID-19 outbreak
We investigate adaptive strategies to robustly and optimally control the COVID-19 pandemic via social distancing measures based on the example of Germany. Our goal is to minimize the number of fatalities over the course of two years without inducing excessive social costs. We consider a tailored model of the German COVID-19 outbreak with different parameter sets to design and validate our approach. Our analysis reveals that an open-loop optimal control policy can significantly decrease the number of fatalities when compared to simpler policies under the assumption of exact model knowledge. In a more realistic scenario with uncertain data and model mismatch, a feedback strategy that updates the policy weekly using model predictive control (MPC) leads to a reliable performance, even when applied to a validation model with deviant parameters. On top of that, we propose a robust MPC-based feedback policy using interval arithmetic that adapts the social distancing measures cautiously and safely, thus leading to a minimum number of fatalities even if measurements are inaccurate and the infection rates cannot be precisely specified by social distancing. Our theoretical findings support various recent studies by showing that (1) adaptive feedback strategies are required to reliably contain the COVID-19 outbreak, (2) well-designed policies can significantly reduce the number of fatalities compared to simpler ones while keeping the amount of social distancing measures on the same level, and (3) imposing stronger social distancing measures early on is more effective and cheaper in the long run than opening up too soon and restoring stricter measures at a later time.
A Review of Current State-of-the-Art Control Methods for Lower-Limb Powered Prostheses
Lower-limb prostheses aim to restore ambulatory function for individuals with lower-limb amputations. While the design of lower-limb prostheses is important, this paper focuses on the complementary challenge - the control of lower-limb prostheses. Specifically, we focus on powered prostheses, a subset of lower-limb prostheses, which utilize actuators to inject mechanical power into the walking gait of a human user. In this paper, we present a review of existing control strategies for lower-limb powered prostheses, including the control objectives, sensing capabilities, and control methodologies. We separate the various control methods into three main tiers of prosthesis control: high-level control for task and gait phase estimation, mid-level control for desired torque computation (both with and without the use of reference trajectories), and low-level control for enforcing the computed torque commands on the prosthesis. In particular, we focus on the high- and mid-level control approaches in this review. Additionally, we outline existing methods for customizing the prosthetic behavior for individual human users. Finally, we conclude with a discussion on future research directions for powered lower-limb prostheses based on the potential of current control methods and open problems in the field.